Bao Yanqing, Tian Mingxing, Li Peng, Liu Jiameng, Ding Chan, Yu Shengqing
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Shanghai, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Vet Res. 2017 Apr 4;48(1):17. doi: 10.1186/s13567-017-0422-9.
Brucellosis, caused by Brucella spp., is an important zoonosis worldwide. Vaccination is an effective strategy for protection against Brucella infection in livestock in developing countries and in wildlife in developed countries. However, current vaccine strains including S19 and RB51 are pathogenic to humans and pregnant animals, limiting their use. In this study, we constructed the Brucella abortus (B. abortus) S2308 mutant strain Δ22915, in which the putative lytic transglycosylase gene BAB_RS22915 was deleted. The biological properties of mutant strain Δ22915 were characterized and protection of mice against virulent S2308 challenge was evaluated. The mutant strain Δ22915 showed reduced survival within RAW264.7 cells and survival in vivo in mice. In addition, the mutant strain Δ22915 failed to escape fusion with lysosomes within host cells, and caused no observable pathological damage. RNA-seq analysis indicated that four genes associated with amino acid/nucleotide transport and metabolism were significantly upregulated in mutant strain Δ22915. Furthermore, inoculation of ∆22915 at 10 colony forming units induced effective host immune responses and long-term protection of BALB/c mice. Therefore, mutant strain ∆22915 could be used as a novel vaccine candidate in the future to protect animals against B. abortus infection.
由布鲁氏菌属引起的布鲁氏菌病是一种在全球范围内重要的人畜共患病。疫苗接种是发展中国家保护家畜以及发达国家保护野生动物免受布鲁氏菌感染的有效策略。然而，包括S19和RB51在内的当前疫苗株对人类和怀孕动物具有致病性，限制了它们的使用。在本研究中，我们构建了流产布鲁氏菌（B. abortus）S2308突变株Δ22915，其中假定的溶菌转糖基酶基因BAB_RS22915被删除。对突变株Δ22915的生物学特性进行了表征，并评估了其对小鼠抵抗强毒株S2308攻击的保护作用。突变株Δ22915在RAW264.7细胞内的存活率降低，在小鼠体内的存活率也降低。此外，突变株Δ22915无法逃脱与宿主细胞内溶酶体的融合，并且未造成可观察到的病理损伤。RNA测序分析表明，与氨基酸/核苷酸转运和代谢相关的四个基因在突变株Δ22915中显著上调。此外，以10个菌落形成单位接种Δ22915可诱导有效的宿主免疫反应并对BALB/c小鼠提供长期保护。因此，突变株Δ22915未来可作为一种新型疫苗候选物用于保护动物免受流产布鲁氏菌感染。
